U.S. Pat. No. 3,939,178 discloses a genus of pyrano [3,4-b]indoles and a method of making them, which include the anti-inflammatory compound 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, also known as etodolac. The method which is generically disclosed, involves reacting 7-ethyltryptophol with methyl 3-oxopentanoate to generate etodolac methyl ester: ##STR1## The etodolac methyl ester may then be converted to etodolac by basic hydrolysis of the ester group, as illustrated at column 1, lines 45-48 and at column 3, lines 39-41 of U.S. Pat. No. 4,585,877: ##STR2##
The synthesis of etodolac described in these patents requires flash chromatographic purification of 7-ethyltryptophol in order to produce etodolac of a pharmaceutical quality (see U.S. Pat. No. 4,585,877, Example 3). However, the use of flash chromatography in industrial scale bulk synthetic reactions is very expensive, time consuming, and cannot be performed on an industrial scale, and is for this reason disfavored.